Effect of endothelins on cytosolic free calcium concentration in neuroblastoma NG108-15 and NCB-20 cells.
The effects of endothelin(ET)-1, ET-2, ET-3 and Big ET on intracellular level of Ca2+ ([Ca2+]i) were studied in neuroblastoma NG108-15 and NCB-20 cells. All ETs, except Big ET, induced an increase in [CA2+]i in NG108-15 cells in a dose-dependent manner, with EC50: 6.7, 11.2 and 71 nM, respectively. However, none of the ET increased [Ca2+]i in NCB-20 cells. Calcium channel blockers diltiazem or nicardipine had no effect on ET-induced increase in [CA2+]i, but extracellular Ca2(+)-depletion significantly reduced the response of NG108-15 cells to ETs. NG108-15 cells exhibited a homologous desensitization to sequential addition of ETs, but no heterologous desensitization among ET, bradykinin and PAF was observed. These data suggest that ET-induced receptor activation results in increased intracellular Ca2+ via a non voltage calcium channel mechanism and intracellular Ca2+ release.
Yue
T L
TL
Department of Pharmacology, Smith Kline Beecham, King of Prussia, PA 19406-0939.
Gleason
M M
MM
Lysko
P G
PG
Feuerstein
G
G
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005470:Fluorometry; D016257:Fura-2 / Q000031:analogs & derivatives; D006706:Homeostasis; D006822:Hybrid Cells / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D016232:Endothelins; D005456:Fluorescent Dyes; C049925:fura-2-am; D009529:Nicardipine; D004110:Diltiazem; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2